{"doi":"10.1002/gepi.21676","title":"SNP Set Association Analysis for Familial Data","abstract":"<jats:p>Genome‐wide association studies (GWAS) are a popular approach for identifying common genetic variants and epistatic effects associated with a disease phenotype. The traditional statistical analysis of such GWAS attempts to assess the association between each individual single‐nucleotide polymorphism (SNP) and the observed phenotype. Recently, kernel machine‐based tests for association between a SNP set (e.g., SNPs in a gene) and the disease phenotype have been proposed as a useful alternative to the traditional individual‐SNP approach, and allow for flexible modeling of the potentially complicated joint SNP effects in a SNP set while adjusting for covariates. We extend the kernel machine framework to accommodate related subjects from multiple independent families, and provide a score‐based variance component test for assessing the association of a given SNP set with a continuous phenotype, while adjusting for additional covariates and accounting for within‐family correlation. We illustrate the proposed method using simulation studies and an application to genetic data from the Genetic Epidemiology Network of Arteriopathy (GENOA) study.</jats:p>","journal":"Genetic Epidemiology","year":2012,"id":19016,"datarank":5.5703288852263375,"base_score":4.709530201312334,"endowment":4.709530201312334,"self_citation_contribution":0.7064295301968502,"citation_network_contribution":4.863899355029488,"self_endowment_contribution":0.7064295301968502,"citer_contribution":4.863899355029488,"corpus_percentile":null,"corpus_rank":null,"citation_count":110,"citer_count":100,"citers_with_citation_signal":89,"citers_with_endowment":89,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":31536,"name":"Michael P. Epstein","orcid":"0000-0001-9647-9738","position":1,"is_corresponding":false},{"id":130106,"name":"Lawrence F. Bielak","orcid":null,"position":2,"is_corresponding":false},{"id":24777,"name":"Min A. Jhun","orcid":null,"position":3,"is_corresponding":false},{"id":14693,"name":"Sharon L. R. Kardia","orcid":"0000-0002-9853-3379","position":4,"is_corresponding":false},{"id":25005,"name":"Patricia A. Peyser","orcid":"0000-0002-9717-8459","position":5,"is_corresponding":false},{"id":41029,"name":"Xihong Lin","orcid":"0000-0001-7067-7752","position":6,"is_corresponding":false},{"id":130105,"name":"Elizabeth D. Schifano","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.709530201312334,"endowment":4.709530201312334,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"22968922","pmcid":"PMC3683469","openalex_id":"https://openalex.org/W1601337698","authors":[],"funders":[{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL087660","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P01 CA134294","title":null},{"funder_name":"NIEHS NIH HHS","grant_id":"T32 ES007142","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL87660","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R35 CA197449","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R37 CA076404","title":null},{"funder_name":"NHGRI NIH HHS","grant_id":"R01 HG003618","title":null},{"funder_name":"NIEHS NIH HHS","grant_id":"T32 ES016645","title":null}],"total_grants":8,"fwci":8.9938,"citation_percentile":0.98295141,"influential_citations":11,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":10},{"year":2014,"count":17},{"year":2015,"count":15},{"year":2016,"count":16},{"year":2017,"count":6},{"year":2018,"count":12},{"year":2019,"count":9},{"year":2020,"count":3},{"year":2021,"count":8},{"year":2022,"count":5},{"year":2023,"count":5},{"year":2024,"count":2}],"oa_status":"green","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://hdl.handle.net/2027.42/94494","host_type":"repository"},{"url":"https://europepmc.org/articles/pmc3683469?pdf=render","host_type":"GREEN"},{"url":"https://hdl.handle.net/2027.42/94494","host_type":"repository"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fgepi.21676","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/gepi.21676","host_type":"publisher"},{"url":"http://hdl.handle.net/2027.42/94494>","host_type":"repository"},{"url":"https://doi.org/10.1002/gepi.21676","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/22968922","host_type":"repository"},{"url":"http://europepmc.org/articles/PMC3683469","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3683469","host_type":"repository"}],"fields_of_study":["Genetic Associations and Epidemiology","Celiac Disease Research and Management","Genetic and phenotypic traits in livestock","Biology","Medicine","Computer Science","Acid Ceramidase","Algorithms","Artificial Intelligence","Chromosomes, Human, Pair 10","Family","Genes","Genetic Association Studies","Genome-Wide Association Study","Humans","Models, Genetic","Phenotype","Polymorphism, Single Nucleotide"],"mesh_terms":["Algorithms","Artificial Intelligence","Chromosomes, Human, Pair 10","Family","Genes","Humans","Models, Genetic","Phenotype","Polymorphism, Single Nucleotide","Genome-Wide Association Study","Acid Ceramidase","Genetic Association Studies"],"keywords":["SNP","Genome-wide association study","Genetic association","Single-nucleotide polymorphism","Epistasis","Covariate","Association test","Genetics","Tag SNP","Biology","Kernel (algebra)","Computational biology","Genotype","Statistics","Mathematics","Gene","Linear Mixed Model","Variance Component Test","Kernel Machine","Score Statistics","Multilocus Test","Family Association Studies","Within-family Correlation"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-04T01:13:52.634344Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}